Sofosbuvir/velpatasvir: A promising combination

Abstract

Hepatitis C virus (HCV) affects 3% of the world population. It represents the main cause of chronic liver disease and is responsible for extra-hepatic complications, such as type 2 diabetes and cardiovascular diseases. HCV includes 7 genotypes differing in the nucleotide sequence variability, the geographic distribution, the rates of viral clearance, the risk of progression to liver fibrosis and to hepatocellular carcinoma, and the response to therapy. Last years have seen remarkable advances in the field of HCV infection with the approval of direct antiviral agents (DAAs) targeting key viral proteins involved in the HCV replication. Several oral regimens combining DAAs from different families have been developed and these regimens showed increased and sustained virological response rates to above 90% reducing the treatment duration to 12 wk or less. In particular, sofosbuvir, a nucleotide analogue nonstructural (NS)5B polymerase inhibitor, and velpatasvir, a NS5A inhibitor, have been tested in two phase 3 trials, the ASTRAL-2 (against HCV genotype 2) and the ASTRAL-3 (against HCV genotype 3), demonstrating to be effective, safe, and well tolerated in patients who were 18 years of age or older and had at least a 6-mo history of HCV infection with a compensated liver disease.

Satisfactory virological response and fibrosis improvement of sofosbuvir-based regimens for Chinese patients with hepatitis C virus genotype 3 infection: results of a real-world cohort study

“…Because SOF is a nucleotide analogue HCV NS5B polymerase inhibitor with similar in vitro activity against all HCV genotypes, several SOF-based regimens have been reported in the therapy of HCV-GT3 patients, including SOF + RBV, SOF + DCV ± RBV, SOF/LDV ± RBV and SOF/VEL [ 8 , 13 , 14 , 16 , 17 , 20 ]. Additionally, DCV also has shown great potency in vitro against HCV GT3.…”

Transporter Expression in Noncancerous and Cancerous Liver Tissue from Donors with Hepatocellular Carcinoma and Chronic Hepatitis C Infection Quantified by LC-MS/MS Proteomics

“…The World Health Organization estimated globally 71 million people had HCV, and over 10,0000 people with HCV died as a result of HCC in 2015 (World Health Organization, 2017). Over 90% of HCV patients treated with direct acting antiviral drug combinations achieve clearance of circulating HCV RNA or a sustained virological response, a result considered to be a functional cure (Bonaventura and Montecucco, 2016;Terrault et al, 2016). Despite this success, the incidence of diagnosis and treatment of HCV is low because up to 90% of people infected are unaware of their infection status (Institute of Medicine Committee on the Prevention and Control of Viral Hepatitis Infection, 2010; Hatzakis et al, 2011).…”

A large-scale computational screen identifies strong potential inhibitors for disrupting SARS-CoV-2 S-protein and human ACE2 interaction

“…Notably, these drugs are primarily used as inhibitors of the hepatitis C virus (HCV) non-structural protein 5 A (NS5A) replication complex. Although the exact mechanism of action of Velpatasvir has not yet been completely determined, it has been reported to bind to domain I of the NS5A protein, inhibiting the activity of the NS5A protein, which results in the disruption of the viral RNA replication complex, blockage of viral HCV RNA production and inhibition of viral replication (Asselah et al, 2018;Bonaventura et al, 2016;Heo & Deeks, 2018). Zafirlukast and pranlukast, both being leukotriene receptor antagonists used for treating chronic asthma (Adkins & Brogden, 1998;Hur et al, 2018;Keam et al, 2003;Yan et al, 2019), had docking score of À8.71 kcal/mol and À8.61 kcal/mol.…”